DEMONSTRATED THAT AMIDOHYDROLASE DOMAIN-CONTAINING 1 GENE IS DIRECTLY ACTIVATED BY THYROID HORMONE AND LIKELY PLAY A ROLE IN THE FORMATION OF ADULT INTESTINAL STEM CELLS DURING XENOPUS METAMORPHOSIS. A tissue-specific microarray analysis of intestinal gene expression during Xenopus laevis metamorphosis has identified a number of candidate stem cell genes. We have carried out detailed analyses of one such gene, amidohydrolase domain containing 1 (AMDHD1) gene, which encodes an enzyme in the histidine catabolic pathway. We show that AMDHD1 is exclusively expressed in the proliferating adult epithelial stem cells during metamorphosis with little expression in other intestinal tissues. We further provide evidence that TH activates AMDHD1 gene expression directly at the transcription level through TH receptor binding to the AMDHD1 gene in the intestine. In addition, our have reported earlier that histidine ammonia-lyase (HAL) gene, another gene in histidine catabolic pathway, is similarly regulated by TH in the intestine. These results together suggest that histidine catabolism plays a critical role in the formation and/or proliferation of adult intestinal stem cells during metamorphosis. REVEALED DISTINCT TRANSFORMATIONS OF INTESTINAL EPITHELIAL CELLS DURING XENOPUS METAMORPHOSIS BY USING MOLECULAR AND CYTOLOGICAL ANALYSES. Earlier studies have revealed a number of cytological and molecular markers for intestinal epithelial cells undergoing different changes during metamorphosis. However, the lack of established double labeling has made it difficult to ascertain the identities of the metamorphosing epithelial cells. We have carried out different double staining with a number of cytological and molecular markers during TH-induced and natural metamorphosis in Xenopus laevis. Our studies demonstrated conclusively that the clusters of proliferating cells in the epithelium at the climax of metamorphosis are undifferentiated epithelial cells and express the well-known adult intestinal stem cell marker gene Lgr5. We further show that the adult stem cells and apoptotic larval epithelial cells are distinct epithelial cells during metamorphosis. Our findings suggest that morphologically identical larval epithelial cells choose two alternative paths: programmed cell death or dedifferentiation to form adult stem cells, in response to TG during metamorphosis with apoptosis occurring prior to the formation of the proliferating adult stem cell clusters (islets).